Phase I study of capecitabine, oxaliplatin, bevacizumab, and everolimus in advanced solid tumors.
Phase I study of capecitabine, oxaliplatin, bevacizumab, and everolimus in advanced solid tumors.
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DOI：
10.1007/s10637-014-0089-2
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发表时间：
2014-08
影响因子：
3.4
通讯作者：
Hurwitz, Herbert I.
中科院分区：
文献类型：
--
作者：
Rangwala, Fatima;Bendell, Johanna C.;Kozloff, Mark F.;Arrowood, Christy C.;Dellinger, Andrew;Meadows, Jennifer;Tourt-Uhlig, Sandra;Murphy, Jennifer;Meadows, Kellen L.;Starr, Aijing;Broderick, Samuel;Brady, John C.;Cushman, Stephanie M.;Morse, Michael A.;Uronis, Hope E.;Hsu, S. David;Zafar, S. Yousuf;Wallace, James;Starodub, Alexander N.;Strickler, John H.;Pang, Herbert;Nixon, Andrew B.;Hurwitz, Herbert I.
确定卡培他滨、奥沙利铂、贝伐单抗和依维莫司在晚期实体瘤患者中的最大耐受剂量（MTD）、毒性和药效学。这是一个标准的“3+3”剂量递增试验。所有受试者在每个周期的第一天接受贝伐单抗7.5mg/kg。卡培他滨、奥沙利铂和依维莫司的剂量每剂量限制毒性（DLT）被修改。分析基线和治疗时血浆生物标志物。评估存档的肿瘤NRP1、NRP2和VEGF-A亚型的mRNA水平。29例可评价毒性，30例可评价疗效。在队列1中观察到2例DLT，在队列1和-1b中各观察到1例DLT。≥3级的毒性包括中性粒细胞减少、高血压、穿孔/瘘/出血、高甘油三酯血症、腹泻和血栓栓塞。12名受试者出现部分反应（PR）；12例病情稳定为最佳反应。7名化疗难治性转移性结直肠癌（mCRC）患者中有3名经历了PR；15例化疗性mCRC患者中有8例发生PR。治疗后血浆TβRIII和IL-6升高，但与预后无关。增加的VEGF165水平与更长的无进展生存期显著相关。依维莫司联合全剂量卡培他滨、奥沙利铂和贝伐单抗具有不可接受的毒性。每日依维莫司5mg；卡培他滨680mg/m2 BID d 1-14；奥沙利铂100mg/m2，贝伐单抗7.5mg/kg，第一天。mCRC有活性。
To define maximum tolerated dose (MTD), toxicities, and pharmacodynamics of capecitabine, oxaliplatin, bevacizumab, and everolimus in advanced solid tumor patients. This was a standard “3+3” dose-escalation trial. All subjects received bevacizumab 7.5mg/kg on day one of each cycle. Doses for capecitabine, oxaliplatin and everolimus were modified per dose limiting toxicity (DLT). Baseline and on-treatment plasma biomarkers were analyzed. Archived tumor mRNA levels were evaluated for NRP1, NRP2 and VEGF-A isoforms. Twenty-nine patients were evaluable for toxicity and 30 for efficacy. Two DLTs were observed in cohort 1 and one DLT each was observed in cohort -1 and -1b. Grade ≥3 toxicities included neutropenia, hypertension, perforation/fistula/hemorrhage, hypertriglyceridemia, diarrhea, and thromboembolism. Twelve subjects experienced partial response (PR); 12 had stable disease as best response. Three of seven chemorefractory metastatic colorectal cancer (mCRC) subjects experienced PR; eight of 15 chemonaive mCRC subjects experienced PR. Plasma TβRIII and IL-6 increased on treatment but without correlation to outcome. Increased VEGF165 levels significantly correlated with longer progression free survival. Everolimus with full dose capecitabine, oxaliplatin, and bevacizumab had unacceptable toxicity. MTD was: everolimus 5mg daily; capecitabine 680mg/m2 BID days 1-14; oxaliplatin 100mg/m2 and bevacizumab 7.5mg/kg, day one. Activity was noted in mCRC.
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影响因子：
168.9
作者：
Escudier, Bernard;Pluzanska, Anna;Moore, Nicola
通讯作者：
Moore, Nicola
影响因子：
3
作者：
O'Reilly, Terence;Lane, Heidi A.;McSheehy, Paul M. J.
通讯作者：
McSheehy, Paul M. J.
DOI：
10.1038/nrc2442
发表时间：
2008-08
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.8
作者：
Gatza CE;Oh SY;Blobe GC
通讯作者：
Blobe GC
影响因子：
64.8
作者：
Bernardi, Rosa;Guernah, Ilhem;Pandolfi, Pier Paolo
通讯作者：
Pandolfi, Pier Paolo